tbuckley/cabot-search huggingface dataset:
A systematic review and meta-analysis of intensive treatment options for adults with eating disorders
Authors: Kathleen de Boer, Catherine Johnson, Tracey D. Wade, Marcela Radunz, Anne Nileshni Fernando, Jennifer Babb, Simon Stafrace, Gemma Sharp
Journal: Clinical Psychology Review (2023)

Eating disorders (EDs) are complex conditions with one of the highest mortality rates among psychiatric illnesses. While outpatient evidence-based treatments for EDs in adults exist, there is often utilisation of more intensive interventions as part of treatment. However, a comprehensive analysis of the impacts of intensive treatment (inpatient, residential and day program) on physical and psychosocial outcomes is lacking. Thus, the current systematic review and meta-analysis aimed to investigate the effectiveness of intensive treatments in adults with EDs for the outcomes of body mass index (BMI), disordered eating, depression, and quality of life, as well as a moderation analysis investigating a range of clinical characteristics. Overall, 62 studies were included in the meta-analysis. The results revealed that intensive treatment in adults yielded significant improvements in BMI (for underweight patients), disordered eating, depression, and quality of life. Treatment setting, length of stay and geographical region of the study all served as moderators for disordered eating and depression. Nevertheless, given the high heterogeneity in the meta- and moderation analyses, these results should be interpreted with caution. Future high-quality research is needed to determine the most beneficial elements of intensive treatment (compared to outpatient) in adults with EDs.
Cisplatin-activated ERβ/DCAF8 positive feedback loop induces chemoresistance in non-small cell lung cancer via PTEN/Akt axis
Authors: Yumeng Hu, Yongjie Xu, Ting Zhang, Qianying Han, Li Li, Mingyang Liu, Ni Li, Genze Shao
Journal: Drug Resistance Updates (2023)

High levels of the estrogen receptor β (ERβ) predict poor prognosis following platinum-containing adjuvant chemotherapies in patients with non-small cell lung cancer (NSCLC). However, the precise role of ERβ remains elusive. In this study, we demonstrated that targeting ERβ could significantly increase the cytotoxicity of cisplatin both in vitro and in vivo. Mechanically, cisplatin directly binds to ERβ, which facilitates its homodimerization and nuclear translocation. ERβ activation transcriptionally represses the expression of DCAF8, an adaptor of CRL4 E3 ubiquitin ligase, which in turn attenuates the proteasomal degradation of ERβ, leading to ERβ accumulation; this positive feedback loop results in Akt activation and eventually cisplatin resistance in NSCLC through PTEN inhibition. Moreover, low expression of DCAF8 and high expression of ERβ are associated with treatment resistance in patients receiving cisplatin-containing adjuvant chemotherapy. The present results provide insights into the underlying mechanism of ERβ-induced cisplatin resistance and offer an alternative therapeutic strategy to improve the efficacy of platinum-based chemotherapy in patients with NSCLC.
Enhancing drug penetration in solid tumors via nanomedicine: Evaluation models, strategies and perspectives
Authors: Xiaoding Shen, Dayi Pan, Qiyong Gong, Zhongwei Gu, Kui Luo
Journal: Bioactive Materials (2023)

Effective tumor treatment depends on optimizing drug penetration and accumulation in tumor tissue while minimizing systemic toxicity. Nanomedicine has emerged as a key solution that addresses the rapid clearance of free drugs, but achieving deep drug penetration into solid tumors remains elusive. This review discusses various strategies to enhance drug penetration, including manipulation of the tumor microenvironment, exploitation of both external and internal stimuli, pioneering nanocarrier surface engineering, and development of innovative tactics for active tumor penetration. One outstanding strategy is organelle-affinitive transfer, which exploits the unique properties of specific tumor cell organelles and heralds a potentially transformative approach to active transcellular transfer for deep tumor penetration. Rigorous models are essential to evaluate the efficacy of these strategies. The patient-derived xenograft (PDX) model is gaining traction as a bridge between laboratory discovery and clinical application. However, the journey from bench to bedside for nanomedicines is fraught with challenges. Future efforts should prioritize deepening our understanding of nanoparticle-tumor interactions, re-evaluating the EPR effect, and exploring novel nanoparticle transport mechanisms.
Time to treat the climate and nature crisis as one indivisible global health emergency
Authors: Kamran Abbasi, Parveen Ali, Virginia Barbour, Thomas Benfield, Kirsten Bibbins-Domingo, Stephen Hancocks, Richard Horton, Laurie Laybourn-Langton, Robert Mash, Peush Sahni, Wadeia Mohammad Sharief, Paul Yonga, Chris Zielinski
Journal:  (2023)
Management of asymptomatic sexually transmitted infections in Europe: towards a differentiated, evidence-based approach
Authors: Chris Kenyon, Björn Herrmann, Gwenda Hughes, Henry J C de Vries
Journal: The Lancet Regional Health - Europe (2023)

Most sexually transmitted infections (STIs) can be accurately diagnosed and treated during asymptomatic carriage. Widespread screening for these STIs is therefore assumed to be an effective way to reduce their prevalence and associated disease. In this review, we provide evidence that this is the case for HIV and syphilis. However, for other STIs such as Neisseria gonorrhoeae and Chlamydia trachomatis, our review reveals that the evidence that screening reduces infection prevalence and associated disease is weak. There is also growing evidence of harms from screening that might outweigh any benefits. The harms include the increased consumption of antimicrobials that follows frequent screening and increased detection of asymptomatic STIs in key populations, such as men who have sex with men taking HIV pre-exposure prophylaxis, and associated risk of antimicrobial resistance in target and non-target organisms. There may also be psycho-social harm associated with an STI diagnosis. We conclude that in the absence of symptoms, in high STI prevalence populations frequent STI screening should be limited to HIV and syphilis.
Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe
Authors: Deniz Gökengin, Teymur Noori, Andrea Alemany, Carlo Bienkowski, Geoffroy Liegon, Ahmet Çağkan İnkaya, Jorge Carrillo, Georg Stary, Katja Knapp, Oriol Mitja, Jean-Michel Molina
Journal: The Lancet Regional Health - Europe (2023)

The current prevention efforts for STIs, HIV and viral hepatitis in the WHO European Region, especially in the Central and Eastern subregions, are hindered by healthcare disparities, data gaps, and limited resources. In this comprehensive narrative review, we aim to highlight both achievements and persisting challenges while also exploring new developments that could significantly impact the prevention of these infections in the near future. While pre-exposure prophylaxis (PrEP) for HIV has been broadly approved and implemented in 38 out of 53 countries in the region, challenges remain, including cost, limited licensing, and incomplete adherence. We explore innovative approaches like on-demand PrEP, long-acting injectable cabotegravir, and intravaginal rings that have shown promising results, alongside the use of six-monthly lenacapavir, the outcomes of which are pending. Additionally, the potential of doxycycline post-exposure prophylaxis has been discussed, revealing efficacy in reducing chlamydia and syphilis risk, but effectiveness against gonorrhoea being contingent on tetracycline resistance rates, and the need of further data to determine potential resistance development in other bacteria and its impact on the gut microbiome. We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
JAK1 promotes HDV replication and is a potential target for antiviral therapy
Authors: Margaux J. Heuschkel, Charlotte Bach, Laura Meiss-Heydmann, Emma Gerges, Emanuele Felli, Fabio Giannone, Patrick Pessaux, Catherine Schuster, Julie Lucifora, Thomas F. Baumert, Eloi R. Verrier
Journal: Journal of Hepatology (2023)

Background & Aims Liver chronic co-infection with hepatitis B and D viruses (HBV and HDV) is the most aggressive form of chronic viral hepatitis. To date, no treatment allows efficient viral clearance, and a better characterization of virus-host interactions is required to develop new therapeutic strategies. Methods Using loss-of-function strategies, we validated the unexpected proviral activity of the innate immune-related Janus kinase 1 (JAK1) in the HDV life cycle and determined its mechanism of action on HDV through various functional analyses including co-immunoprecipitation assays. Results We confirmed the key role of JAK1 kinase activity in HDV infection. Moreover, our results suggest that JAK1 inhibition is associated with a modulation of ERK1/2 activation and S-HDAg phosphorylation, crucial for viral replication. Finally, we showed that FDA-approved JAK1-specific inhibitors are efficient antivirals in relevant in vitro models including primary human hepatocytes. Conclusions Taken together, we uncovered JAK1 as a key host factor for HDV replication and a potential target for new antiviral treatment. Impact and Implications Chronic hepatitis D is the most aggressive form of chronic viral hepatitis with no curative treatment. New therapeutic strategies based on host targeting agents are urgently needed. Here, using loss-of-function strategies, we uncover an unexpected interaction between JAK1, a major actor of the innate antiviral response, and HDV infection. We demonstrated that JAK1 kinase activity is crucial for both the phosphorylation of the delta antigen and the replication of the virus. By demonstrating the antiviral potential of several FDA-approved JAK1 inhibitors, our results could pave the way to the development of innovative therapeutic strategies to tackle this global health threat.
Chromatin accessibility analysis and architectural profiling of human kidneys reveal key cell types and a regulator of diabetic kidney disease
Authors: Minho Eun, Donggun Kim, So-I Shin, Hyun Oh Yang, Kyoung-Dong Kim, Sin Young Choi, Sehoon Park, Dong Ki Kim, Chang Wook Jeong, Kyung Chul Moon, Hajeong Lee, Jihwan Park
Journal: Kidney International (2023)
Five-Year Survival Outcomes After Carbon-Ion Radiotherapy for Operable Stage I NSCLC: A Japanese National Registry Study (J-CROS-LUNG)
Authors: Nobuteru Kubo, Hiroaki Suefuji, Mio Nakajima, Sunao Tokumaru, Naoko Okano, Daisaku Yoshida, Osamu Suzuki, Hitoshi Ishikawa, Miyako Satouchi, Haruhiko Nakayama, Kimihiro Shimizu, Yoshiyuki Shioyama
Journal: Journal of Thoracic Oncology (2023)

Introduction: The standard therapy for stage I non-small cell lung cancer (NSCLC) is surgery, but some operable patients refuse this option and instead undergo radiotherapy.Carbon-ion radiotherapy (CIRT) is a type of radiotherapy.The Japanese prospective nationwide registry study on CIRT began in 2016.Here, we analyzed real-world clinical outcomes of CIRT for operable patients with stage I NSCLC.Methods: All patients with operable stage I NSCLC treated with CIRT in Japan between 2016 and 2018 were enrolled.The dose fractionations for CIRT were selected from several options approved by the Japanese Society for Radiation Oncology.CIRT was delivered to the primary tumor, not to lymph nodes.Results: The median follow-up period was 56 months.Among 136 patients, 117 (86%) had clinical stage IA NSCLC, and 19 (14%) had clinical stage IB NSCLC.Fifty (37%) patients were diagnosed clinically without having been diagnosed histologically.Most tumors (97%) were located in the periphery.The 5-year overall survival, cause-specific survival, progression-free survival, and local control rate were 81.8% (95% CI, 75.1-89.2),91.2% (95% CI, 86.0-96.8),65.9% (95% CI, 58.2-74.6), and 95.8% (95% CI, 92.3-99.5),respectively.Multivariate analysis identified age as a significant factor for overall survival, whereas age and consolidation/tumor ratio were significant factors for progression-free survival.There was no grade 4 or higher toxicity.Grade 3 radiation pneumonitis occurred in one patient.Conclusions: This study reports the long-term outcomes of CIRT for operable NSCLC in the realworld.CIRT for operable patients showed favorable outcomes, with tolerable toxicity.
Curiosity-driven exploration: foundations in neuroscience and computational modeling
Authors: Alireza Modirshanechi, Kacper Kondrakiewicz, Wulfram Gerstner, Sebastian Haesler
Journal: Trends in Neurosciences (2023)

Curiosity refers to the intrinsic desire of humans and animals to explore the unknown, even when there is no apparent reason to do so. Thus far, no single, widely accepted definition or framework for curiosity has emerged, but there is growing consensus that curious behavior is not goal-directed but related to seeking or reacting to information. In this review, we take a phenomenological approach and group behavioral and neurophysiological studies which meet these criteria into three categories according to the type of information seeking observed. We then review recent computational models of curiosity from the field of machine learning and discuss how they enable integrating different types of information seeking into one theoretical framework. Combinations of behavioral and neurophysiological studies along with computational modeling will be instrumental in demystifying the notion of curiosity.
Single-cell analysis of immune recognition in chronic myeloid leukemia patients following tyrosine kinase inhibitor discontinuation
Authors: Jani Huuhtanen, Shady Adnan-Awad, Jason Theodoropoulos, Sofia Forstén, Rebecca Warfvinge, Olli Dufva, Jonas Bouhlal, Parashar Dhapola, Hanna Duàn, Essi Laajala, Tiina Kasanen, Jay Klievink, Mette Ilander, Taina Jaatinen, Ulla Olsson-Strömberg, Henrik Hjorth-Hansen, Andreas Burchert, Göran Karlsson, Anna Kreutzman, Harri Lähdesmäki, Satu Mustjoki
Journal: Leukemia (2023)

Abstract Immunological control of residual leukemia cells is thought to occur in patients with chronic myeloid leukemia (CML) that maintain treatment-free remission (TFR) following tyrosine kinase inhibitor (TKI) discontinuation. To study this, we analyzed 55 single-cell RNA and T cell receptor (TCR) sequenced samples (scRNA+TCRαβ-seq) from patients with CML ( n = 13, N = 25), other cancers ( n = 28), and healthy ( n = 7). The high number and active phenotype of natural killer (NK) cells in CML separated them from healthy and other cancers. Most NK cells in CML belonged to the active CD56 dim cluster with high expression of GZMA/B, PRF1, CCL3/4 , and IFNG , with interactions with leukemic cells via inhibitory LGALS9 – TIM3 and PVR – TIGIT interactions. Accordingly, upregulation of LGALS9 was observed in CML target cells and TIM3 in NK cells when co-cultured together. Additionally, we created a classifier to identify TCRs targeting leukemia-associated antigen PR1 and quantified anti-PR1 T cells in 90 CML and 786 healthy TCRβ-sequenced samples. Anti-PR1 T cells were more prevalent in CML, enriched in bone marrow samples, and enriched in the mature, cytotoxic CD8 + T EMRA cluster, especially in a patient maintaining TFR. Our results highlight the role of NK cells and anti-PR1 T cells in anti-leukemic immune responses in CML.
Criteria for Diagnosis and Molecular Monitoring of <i>NPM1</i>-Mutated AML
Authors: Brunangelo Falini, Richard Dillon
Journal: Blood Cancer Discovery (2023)

Abstract NPM1-mutated acute myeloid leukemia (AML) represents the largest molecular subgroup of adult AML. NPM1-mutated AML is recognizable by molecular techniques and immunohistochemistry, which, when combined, can solve difficult diagnostic problems (including identification of myeloid sarcoma and NPM1 mutations outside exon 12). According to updated 2022 European LeukemiaNet (ELN) guidelines, determining the mutational status of NPM1 (and FLT3) is a mandatory step for the genetic-based risk stratification of AML. Monitoring of measurable residual disease (MRD) by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage. Here, we review the criteria for appropriate diagnosis and molecular monitoring of NPM1-mutated AML. Significance: NPM1-mutated AML represents a distinct entity in the 2022 International Consensus Classification and 5th edition of World Health Organization classifications of myeloid neoplasms. The correct diagnosis of NPM1-mutated AML and its distinction from other AML entities is extremely important because it has clinical implications for the management of AML patients, such as genetic-based risk stratification according to 2022 ELN. Monitoring of MRD by qRT-PCR, combined with ELN risk stratification, can guide therapeutic decisions at the post-remission stage, e.g., whether or not to perform allogeneic hematopoietic stem cell transplantation.
Health’s doom loops and why they matter
Authors: Kamran Abbasi
Journal: BMJ (2023)

A "doom loop" means different things in different sectors.It's a term I'm new to, is rarely used in health, but carries an instant attraction.Its application to the climate crisis is most relevant.The climate doom loop refers to how the failure to tackle the climate emergency and its consequences "draws focus and resources from tackling its root causes" (en.wikipedia.org/wiki/Doom_loop). 1 Perhaps doom loops in health deserve more attention.6
Risk Factors for and Risk of Peripheral Artery Disease in Swedish Individuals With Type 2 Diabetes: A Nationwide Register-Based Study
Authors: Tarik Avdic, Hanne K. Carlsen, Rikard Isaksson, Soffia Gudbjörnsdottir, Zacharias Mandalenakis, Stefan Franzén, Naveed Sattar, Joshua A. Beckman, Darren K. McGuire, Björn Eliasson
Journal: Diabetes Care (2023)

To investigate to what extent having control of peripheral artery disease (PAD) risk factors is associated with the risk of incident PAD in individuals with type 2 diabetes.A total of 148,096 individuals with type 2 diabetes in the Swedish National Diabetes Register between 2005 and 2009 were included and matched with 320,066 control subjects on the basis of age, sex, and county. A few control subjects who developed type 2 diabetes after recruitment, during wash-in (<0.2%), were not censored but instead matched with two new control subjects. Individuals with type 2 diabetes were evaluated according to the number of PAD risk factors beyond recommended guideline levels at baseline, including LDL cholesterol, blood pressure, smoking, glycated hemoglobin, and estimated glomerular filtration rate. Incident PAD events were ascertained from 2006 to 2019.A graded association was observed between the number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes. The adjusted hazard ratio for PAD was 1.41 (95% CI 1.23-1.63) for those with type 2 diabetes with all PAD risk factors within target compared with control subjects matched for sex, age, and county but not risk factor status, in contrast with 9.28 (95% CI 3.62-23.79) for those with all five PAD risk factors not at target.A graded association was observed between increasing number of PAD risk factors not at target and incident PAD in individuals with type 2 diabetes.
RNA base editing therapy cures hearing loss induced by OTOF gene mutation
Authors: Yuanyuan Xue, Yong Tao, Xing Wang, Xueling Wang, Yilai Shu, Yuanhua Liu, Wen Kang, Sifan Chen, Zhenzhe Cheng, Boou Yan, Yanwei Xie, Lanting Bi, Haitao Jia, Jinhui Li, Qingquan Xiao, Liying Chen, Xuan Yao, Linyu Shi, Hui Yang, Hao Wu
Journal: Molecular Therapy (2023)
Adiponectin stimulates Sca1+CD34−-adipocyte precursor cells associated with hyperplastic expansion and beiging of brown and white adipose tissue
Authors: Marco Bauzá-Thorbrügge, Milica Vujičić, Belén Chanclón, Vilborg Palsdottir, Nicolas J. Pillon, Anna Benrick, Ingrid Wernstedt Asterholm
Journal: Metabolism (2023)
Getting off tract: contributions of intraorgan microbiota to cancer in extraintestinal organs
Authors: Scott C Thomas, George Miller, Xin Li, Deepak Saxena
Journal: Gut (2023)

The gastrointestinal ecosystem has received the most attention when examining the contributions of the human microbiome to health and disease. This concentration of effort is logical due to the overwhelming abundance of microbes in the gut coupled with the relative ease of sampling compared with other organs. However, the intestines are intimately connected to multiple extraintestinal organs, providing an opportunity for homeostatic microbial colonisation and pathogenesis in organs traditionally thought to be sterile or only transiently harbouring microbiota. These habitats are challenging to sample, and their low microbial biomass among large amounts of host tissue can make study challenging. Nevertheless, recent findings have shown that many extraintestinal organs that are intimately linked to the gut harbour stable microbiomes, which are colonised from the gut in selective manners and have highlighted not just the influence of the bacteriome but that of the mycobiome and virome on oncogenesis and health.